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Biomedical subjects

R Bodmeier

Publications and source records attributed to R Bodmeier.

At least 37 records · Page 2Linked to original sources
PubMed1999

Diffusion-controlled drug delivery systems: calculation of the required composition to achieve desired release profiles.

The aim of this study was to investigate the effect of the composition of diffusion-controlled release devices (type and amount of plasticizer, type of polymer) on the drug diffusivity and the resulting release kinetics in a quantitative way. Diltiazem hydrochloride and theophylline were investigated in ethyl cellulose (EC) and Eudragit((R)) RS 100, plasticized with various amounts of acetyltributyl citrate (ATBC), acetyltriethyl citrate (ATEC), dibutyl phthalate (DBP), dibutyl sebacate (DBS), diethyl phthalate (DEP), and tributyl citrate (TBC). Thin drug-containing films (monolithic solutions) were used to determine the diffusion coefficients experimentally. The effect of the type and amount of plasticizer on the drug diffusivity was found to be significant, whereas the chain length of the polymer only played a minor rule in the investigated systems. Interestingly, a quantitative relationship between the diffusion coefficient of the drug and the plasticizer level could be established. Based on these results, the release kinetics of diffusion-controlled drug delivery systems could be predicted. In this study, the release patterns from microparticles were calculated and the significant effect of the composition of the device on the resulting release rate was simulated. The latter could be effectively modified by varying the type and amount of plasticizer. Independent experiments verified the theoretical predictions. The practical benefit of the presented method is to calculate the required composition of diffusion-controlled drug delivery systems (monolithic solutions) to achieve desired release profiles.

Cellulose↗
PubMed1999

Incorporation of polymeric nanoparticles into solid dosage forms.

Besides parenteral delivery, polymeric nanoparticles have been used for oral drug delivery. In this study, model polymeric nanoparticles (aqueous colloidal polymer dispersions: Eudragit(R) RL 30D, L 30D, NE 30D, or Aquacoat(R)) with different physicochemical properties were incorporated into various solid dosage forms (granules, tablets, pellets or films). The compatibility of the nanoparticles with commonly used tabletting excipients and the redispersibility of the nanoparticles after contact of the solid dosage forms with aqueous media were investigated. Ideally, the nanoparticles should be released from the solid dosage forms with their original properties. The addition of polymeric binders (e.g. polyvinylpyrrolidone, Na carboxymethylcellulose or hydroxypropyl methylcellulose) to the aqueous nanoparticle dispersions prior to wet granulation resulted in phase separation (depletion or bridging flocculation) for many nanoparticle/binder systems. Two critical parameters for the complete redispersibility/release of the nanoparticles with the original particle size properties from the solid dosage forms were a (1) high minimum film formation temperature (MFT) of the polymer dispersion and (2) a good wettability of the dried polymeric nanoparticles. Nanoparticle dispersions with a low MFT were not redispersible, they coalesced into larger agglomerates/films during the drying step. Contact angle measurements correlated well with the redispersibility of the nanoparticles, with ethylcellulose particles having high contact angles and poor redispersibility and Eudragit(R) RL, a polymer stabilized with quaternary ammonium groups, having low contact angles and good redispersibility.

Acrylic Resins↗
PubMed1999

Drug release from beads coated with an aqueous colloidal ethylcellulose dispersion, Aquacoat, or an organic ethylcellulose solution.

The objective was to investigate several factors (composition of the coating formulation, the type and pH of the release medium and curing conditions), which influence the drug release from beads coated with either the aqueous ethylcellulose dispersion, Aquacoat or an organic ethylcellulose solution. The chlorpheniramine maleate release from Aquacoat-coated beads was faster in pH 7.4 buffer than in 0.1 N HCl. Increasing the curing time and curing temperature decreased the drug release in pH 7.4 buffer but did not affect the release in 0.1 N HCl. In contrast, the drug release from beads coated with the ethanolic ethylcellulose solution was not affected by the curing step, the release medium or the addition of sodium lauryl sulfate. Scanning electron microscopy and contact angle measurements explained the release data. The differences in the drug release behavior of aqueous--and organic solvent--ethylcellulose--coated beads could be attributed to the differences in the film formation process.

Cellulose↗
PubMed1999

Tackiness of acrylic and cellulosic polymer films used in the coating of solid dosage forms.

The objective was to determine the tackiness of acrylic and cellulosic polymer films in order to make predictions on the tackiness (agglomeration) of coated dosage forms during coating and curing. Force-displacement curves of the detachment process of two polymeric films were used as a measure of tackiness. Various polymers (cellulosic (Aquacoat and acrylics (Eudragit RS 30D, L 30D, NE 30D)), plasticizers (triacetin, triethyl citrate, tributyl citrate, acetyltributyl citrate) and anti-tacking agents (talc and glyceryl monostearate) were investigated. The order of tackiness for films prepared from the different aqueous polymer dispersions was in order of Eudragit NE 30D > RS 30D > RL 30D > Aquacoat. The tackiness increased with increasing plasticizer concentration due to the softening of the polymer. A correlation between the minimum film formation temperature and the tackiness was observed, however, no correlation between the tackiness and the lipophilicity of the plasticizer was seen. Talc and glyceryl monostearate (GMS) reduced the tackiness of the films significantly, with GMS being effective at much lower concentrations. Curing of Eudragit RS 30D-coated theophylline beads at temperatures higher than 40 degrees C in an irreversible agglomeration of the beads and damage of the coating upon separation of the beads. This resulted in a faster release than with uncured beads. Blending the beads with talc just prior to the curing step eliminated the agglomeration and therefore film damage, even at a curing temperature of 60 degrees C.

Acrylates↗
PubMed1999

A new model describing the swelling and drug release kinetics from hydroxypropyl methylcellulose tablets.

A novel mathematical model for the water transport into and drug release from hydroxypropyl methylcellulose (HPMC) tablets is presented. Fick's second law of diffusion is used to describe the mass transfer processes in the three-component system drug/polymer/water. Numerical solutions of the respective set of partial differential equations are provided, considering axial and radial diffusion within cylindrical tablets. It is shown that the diffusion coefficients strongly depend on the water concentration (parameters quantifying this dependence have been determined). Swelling of the device is considered using moving boundary conditions, whereas dissolution processes are neglected. Experiments proved the applicability of the theory. The practical benefit of the new model is to calculate the required shape and dimensions of HPMC tablets to achieve a desired release profile.

Algorithms↗
PubMed1999

HPMC-matrices for controlled drug delivery: a new model combining diffusion, swelling, and dissolution mechanisms and predicting the release kinetics.

PURPOSE: The purpose of this study was to investigate the drug release mechanisms from hydroxypropyl methylcellulose (HPMC)-matrices, and to develop a new model for quantitative predictions of controlled drug delivery. METHODS: The dissolved mass of pure HPMC-matrices and the drug release rate from propranolol HCl-loaded HPMC-matrices were determined experimentally. Based on Fick's second law of diffusion for cylinders, the transport of water and drug were modeled considering (i) both radial and axial diffusion, (ii) concentration-dependent drug diffusivities, (iii) matrix swelling and (iv) HPMC dissolution. RESULTS: Good agreement between theory and experiment (dissolved mass and drug release studies) was obtained, proving the validity of the presented model. The water and drug diffusivities are strongly dependent on the matrix swelling ratio. Diffusion, swelling and dissolution are the governing mechanisms involved in the overall drug release process. CONCLUSIONS: The practical benefit of the presented model is to identify the required shape and dimensions of drug-loaded HPMC-matrices in order to achieve desired release profiles, thus facilitating the development of new controlled drug delivery products. This will be demonstrated in a future study.

Delayed-Action Preparations↗
PubMed1999

Evaluation of an enzyme-containing capsular shaped pulsatile drug delivery system.

PURPOSE: To develop an enzymatically-controlled pulsatile drug release system based on an impermeable capsule body, which contains the drug and is closed by an erodible pectin/pectinase-plug. METHODS: The plug was prepared by direct compression of pectin and pectinase in different ratios. In addition to the disintegration times of the plugs, the lag times and the release profiles of the pulsatile system were determined as a function of pectin:enzyme ratio, the pH of the surrounding medium, and the addition of buffering or chelating agents. RESULTS: The disintegration time of the plug, respectively the lag time prior to the drug release was controlled by the pectin:enzyme ratio and the plug weight. The inclusion of a buffering agent within the plug lead to a plug disintegration independent of the surrounding pH. The addition of N(alpha)-EDTA hindered the formation of non-soluble calcium pectinate in the presence of calcium ions in the environment. The addition of effervescent agents to the capsule content resulted in a rapid emptying of the capsule content after plug degradation. CONCLUSIONS: A pulsatile drug delivery system based on an erodible pectin plug containing a pectinolytic enzyme was developed. The drug release was controlled by the enzymatic degradation and dissolution of pectin.

Administration, Oral↗
PubMed1998

Biodegradable, somatostatin acetate containing microspheres prepared by various aqueous and non-aqueous solvent evaporation methods.

Somatostatin, a therapeutic peptide drug, was entrapped within polymeric microspheres made from high molecular weight poly (D,L-lactide/glycolide) (PLGA) or low molecular weight poly (D,L-lactide) (PLA) by various modifications of the O/W-solvent evaporation method. The drug was either dispersed as solid (dispersion method), dissolved with the aid of a co-solvent (co-solvent method) or emulsified as an aqueous solution (W/O/W-multiple emulsion method) in the organic polymer solution prior to emulsification into an external aqueous phase. Additionally, a non-aqueous O/O-method was evaluated for the formation of the microspheres. Acceptable encapsulation efficiencies were obtained with all methods, regardless of the physical state of drug and the polymer type. The total volume of organic solvent and the co-solvent content were found to be important preparation factors of the O/W-co-solvent method. A more lipophilic solvent system appeared to favor efficient drug encapsulation. Replacing the widely used but toxic methylene chloride with ethyl acetate resulted in significantly lower drug loadings. The preparation method substantially affected the morphology of the microspheres and the drug release.

Biocompatible Materials↗
PubMed1998

Effect of ion exchange resins on the drug release from matrix tablets.

Ion exchange resins were incorporated into hydroxypropylmethylcellulose (HPMC) matrix tablets to modify the release of oppositely charged drugs. The drug release from HPMC tablets containing drug-resin complexes was significantly slower than from HPMC tablets containing drug without resin. A physical mixture of drug and ion exchange resin (cationic drug, propranolol HCl, with the cation exchange resin, Amberlite IRP 69, or the anionic drug, sodium diclofenac, with the anion exchange resin, cholestyramine (Duolite ATP-143)) resulted in almost the same drug release as tablets containing preformed drug-resin complexes. Upon contact with the dissolution medium, a gel layer formed rapidly around the solid tablet core and the complex between the drug and the resin formed in situ within the gelled regions. No effect of pH of the dissolution medium (0.1 N HCl or pH 7.4 phosphate buffer) or resin counterion was observed with the strong cation exchanger, Amberlite IRP 69. The resin was dissociated at both pH-values, allowing drug binding. With the weak cation exchange resin, Amberlite IRP 88, in situ complex formation and retardation was only observed in pH 7.4 buffer but not in 0.1 N HCl because of the non-ionization of the carboxyl groups. The drug release depended also on the amount and particle size of the resin particles and the type of carrier. The use of smaller resin particles eliminated the burst release seen with larger resin particles. Upon comparing different carrier materials, a rapid formation of the gel layer was important for the in situ complex formation. The drug release was in the order of Gelucire 54/02 (glyceryl palmitostearate) > polyethylene oxide 400K > HPMC K15M.

Adrenergic beta-Antagonists↗
PubMed1998

Calculation of the dimensions of drug-polymer devices based on diffusion parameters.

The release kinetics of a polymeric-controlled release device are determined by its geometry and dimensions. A method to calculate the required size and shape of diffusion-controlled dosage forms to achieve a particular release profile is presented. The diffusion parameters are determined for various drugs (theophylline, diltiazem hydrochloride and caffeine) with thin ethyl cellulose (EC) films, containing different plasticizers [dibutyl sebacate (DBS) and acetyl tributyl citrate (ATBC)]. Computer simulations are then used to predict the drug release kinetics from various dosage forms (e.g. microparticles and cylinders). The practical benefit of these simulations is to optimize the geometry and dimensions of a controlled release device without the need of experimental studies. To verify the theoretical predictions, the release kinetics of theophylline from EC/ATBC microparticles of different size have also been determined experimentally. Good agreement is found between theory and experiment, proving the validity of the presented method.

Chemistry, Pharmaceutical↗
PubMed1998

Pulsatile drug release from an insoluble capsule body controlled by an erodible plug.

PURPOSE: The objective of this study was to develop and evaluate a pulsatile drug delivery system based on an impermeable capsule body filled with drug and an erodible plug placed in the opening of the capsule body. METHODS: The erodible plugs were either prepared by direct compression followed by placing the tablets in the capsule opening or by congealing a meltable plug material directly within the capsule opening. The disintegration/erosion properties of these plugs were determined and optimized for the final delivery system. In order to assure rapid drug release of the capsule content after erosion of the plug, various excipients (fillers, effervescent agents) and drugs with different solubilities were evaluated. The lag time prior to drug release and the subsequent drug release were investigated as function of capsule content, plug composition, plug preparation technique, plug hardness, weight, and thickness. RESULTS: The erosion time of the compressed plugs increased with increasing molecular weight of the hydrophilic polymer (e.g. hydroxypropyl methylcellulose, polyethylene oxide), decreasing filler (lactose) content and decreased with congealable lipidic plugs with increasing HLB-value and inclusion on surfactants. For complete and rapid release of the drug from the capsule body, effervescent agents had to be included in the capsule content. The drug delivery system showed typical pulsatile release profiles with a lag time followed by a rapid release phase. The lag time prior to the pulsatile drug release correlated well with the erosion properties of the plugs and, besides the composition of the plug, could be controlled by the thickness (weight) of the plug. CONCLUSIONS: A single-unit, capsular-shaped pulsatile drug delivery system was developed wherein the pulsatile release was controlled by the erosion properties of a compressed or congealed plug placed within the opening of the capsule opening.

Capsules↗
PubMed1997

Swelling of and drug release from monoglyceride-based drug delivery systems.

Depending on the water content, unsaturated monoglycerides form various liquid crystalline phases, which can be used as sustained-release carriers. The aim of this study was to investigate the water uptake of and drug release from melt-congealed monoglyceride-based drug carriers. The water uptake of the unsaturated monoglycerides monoolein and monolinolein followed second-order swelling kinetics and levelled off at about 50% water content, at which a highly viscous cubic phase was formed. The rapid formation of the cubic phase suggested that the drug release occurred mainly from this phase. The drug release followed the square-root of time relationship during the initial release phase. Chlorpheniramine maleate, an amphiphilic drug was not completely released because of binding to the cubic phase. The rate of water uptake increased and the maximum water uptake decreased with increasing temperature. The drug release could be controlled by varying the surface-to-volume ratio, the drug loading, and the water content of the lipid matrix. It was independent of the source of monoolein.

Calorimetry, Differential Scanning↗
PubMed1997

Microencapsulation of antimicrobial ceftiofur drugs.

Polymeric microparticles containing two ceftiofur salts as antimicrobial agents for intramammary application in dry cows were prepared by modified o/w-solvent evaporation methods (dispersion or cosolvent method) or by a w/o/w-multiple emulsion solvent evaporation method. The microspheres were characterized with respect to drug loading, drug release, and morphological properties. The three methods resulted in high encapsulation efficiencies. The choice of organic solvent/solvent mixture strongly affected the structure of the microparticles; both matrix and reservoir-type structures with different porosities were obtained. Scaling up to larger batch sizes resulted in microspheres with a faster drug release. The addition of water-miscible cosolvents to the water-immiscible polymer solution allowed the preparation of microparticles from a drug solution rather than a drug dispersion. Microparticles prepared by the cosolvent method could be separated after shorter time intervals from the aqueous phase; the microspheres had a denser matrix with finely dispersed drug crystals and a slower drug release when compared with microspheres prepared by the dispersion method, which had a more porous structure with larger embedded drug crystals. The cosolvent and dispersion methods present a simple alternative to the w/o/w-solvent evaporation method for the encapsulation of water-soluble drugs with an external water phase.

Cephalosporins↗
PubMed1996

The influence of buffer species and strength on diltiazem HCl release from beads coated with the aqueous cationic polymer dispersions, Eudragit RS, RL 30D.

PURPOSE: Eudragit RL and RS 30D are pseudolatexes frequently used in the coating of solid dosage forms. They are based on cationic copolymers stabilized with quaternary ammonium groups (poly(ethylacrylate-methylmethacrylate-trimethylammonioethyl methacrylate chloride). A pH-independent drug release is expected because of the quaternary nature of the cationic groups. The objective was to explain a distinct "pH-dependent" drug release in various buffer media with coated diltiazem beads. METHODS: The diltiazem HCl release from and water uptake of Eudragit RS/RL-coated beads was determined in various buffers of different buffer species, pH or concentration. RESULTS: The drug release in the different buffer media was in the following order: pH 5.0 acetate > pH 3.5 formate > pH 7.4 phosphate buffer > 0.1M HCl). This "pH-dependent" drug release could be explained with an anion exchange process; the chloride counterions of the quaternary groups were exchanged with the anionic buffer species during the dissolution study. The water uptake of the coated beads correlated well with the drug release from the beads. Increasing the buffer strength (acetate buffer) first increased and then decreased the drug release, while increasing the ionic strength of different buffers with NaCl decreased the drug release and eliminated the observed buffer effects because of the excess of chloride ions. CONCLUSIONS: The anionic buffer species and not the pH had a significant effect on the hydration and hence on the drug release from beads coated with the cationic polymers, Eudragit RS and RL.

Acrylic Resins↗
PubMed1995

Polymeric microspheres prepared by spraying into compressed carbon dioxide.

PURPOSE: The objective was to prepare polymeric microparticles by atomizing organic polymer solutions into a spray chamber containing compressed CO2 (PCA-process) and to study the influence of various process parameters on their morphological characteristics. METHOD: The swelling of various pharmaceutically acceptable polymers [ethyl cellulose, poly(methyl methacrylate), poly(epsilon-caprolactone), poly(dl-lactide), poly(l-lactide) and poly(dl-lactide-glycolide) copolymers] in CO2 was investigated in order to find polymers which did not agglomerate during the spraying process. Poly(l-lactide) (L-PLA) microparticles were prepared by spraying the organic polymer solution into CO2 in a specially designed spraying apparatus. The effect of various process (pressure and temperature of the CO2 phase, flow rate) and formulation (polymer concentration) variables on the morphology and particle size of L-PLA-microparticles was investigated. RESULTS: Polymers with low glass transition temperatures agglomerated even at low temperatures. The formation of microparticles was favored at moderate temperatures, low polymer concentrations, high pressures and high flow rates of CO2. High polymer concentrations and low flow rates resulted in the formation of polymeric fibers. Colloidal L-PLA particles could also be prepared with this technique in a surfactant-free environment. Initial studies on the microencapsulation of drugs resulted in low encapsulation efficiencies. CONCLUSIONS: The PCA method is a promising technique for the preparation of drug-containing microparticles. Potential advantages of this method include the flexibility of preparing microparticles of different size and morphology, the elimination of surfactants, the minimization of residual organic solvents, low to moderate processing temperatures and the potential for scale-up.

Carbon Dioxide↗
PubMed1994

Mechanical properties of dry and wet cellulosic and acrylic films prepared from aqueous colloidal polymer dispersions used in the coating of solid dosage forms.

The mechanical properties of dry and wet polymeric films prepared from various aqueous polymeric dispersions were evaluated by a puncture test. They were studied with respect to type of polymer dispersion [cellulosic: Aquacoat and Surelease; acrylic: Eudragit NE, L, RS, and RL 30 D], plasticizer type (water-soluble or water-insoluble), drying or curing conditions, method of film preparation (pseudolatex-vs solvent casting) and ratio of Eudragit RS/RL 30 D in mixed Eudragit RS/RL films. Dry and wet mechanical strengths of the polymeric films depended primarily on the types of the colloidal polymer dispersion and the plasticizer. Films prepared from ethylcellulose dispersions resulted in very weak and brittle films when compared to the acrylic films. Pseudolatex-cast ethylcellulose films showed lower puncture strength and elongation values when compared to those of the solvent-cast films. Curing of the pseudolatex-cast ethylcellulose films had minimal effects on their mechanical properties. Eudragit L 30D, an enteric polymer dispersion, resulted in brittle films in the dry state, but in very flexible films in the wet state because of the plasticization effect of water. Wet Eudragit RS 30 D polymer films plasticized with water-insoluble plasticizers were significantly more flexible than the corresponding wet films plasticized with water-soluble plasticizers. The water-soluble plasticizers leached from the films during exposure to the aqueous medium, while the water-insoluble plasticizers were almost completely retained within the wet films. The low permeability of a water-soluble drug, chlorpheniramine maleate, and the weak mechanical properties of Aquacoat films could suggest osmotic driven/rupturing effects as the release mechanisms from Aquacoat-coated dosage forms.

Acrylates↗
PubMed1993

Microencapsulation of drugs with aqueous colloidal polymer dispersions.

Sustained-release polymer particles containing drugs with various solubility characteristics (ibuprofen, theophylline, guaifenesin, and pseudoephedrine HCl) were prepared with colloidal polymer dispersions in a completely aqueous environment as an alternative to conventional microencapsulation techniques, which use organic solvents. Spherical particles were prepared by spraying or dropping dilute sodium alginate solutions (0.67%, w/w) containing the dissolved or dispersed drug and colloidal polymer particles into calcium chloride solutions. The gelled particles, which formed by ionotropic gelation of the polysaccharide with calcium ions, were dried and cured at 60 degrees C to cause fusion of the colloidal polymer particles into a homogeneous matrix system. Actual drug contents close to 50% and encapsulation efficiencies of between 80 and 98% were achieved with all drugs. Guaifenesin and ibuprofen acted as plasticizers for the ethyl cellulose pseudolatex, whereas with theophylline and pseudoephedrine HCl, dibutyl sebacate had to be added as a plasticizer to yield a nondisintegrating polymer matrix. The stirring time before separation of the particles from the gelation medium had to be minimized with the water-soluble drugs to maximize drug loading; however, it was not critical with the water-insoluble drugs. Drug release was a function of the solubility of the drug, drug loading, and the type of polymer dispersion used.

Capsules↗